We propose to develop a system which can be used to study the ability of environmental pollutants to induce somatic mutagenesis at different loci in animal and plant cells. The methods used to develop this system will be applicable to development of a similar system in other animal or plant cell lines. A series of conditional lethal mutants will be prepared. In the heterozygous form these will appear as pseudo dominant with incomplete penetrance. Inactivation of such mutant loci will result in reversion of the heterozygote to wild type. Such reversions will detect point, deletion, and frameshift mutations. As a result, the mutant strains will provide a sensitive system for the detection of environmentally induced mutations. In such strains somatic crossing-over also should be readily detected, thus allowing a test for agents which increase cross-over rate. The proposal describes: (a) induction of mutants and their selection in heterozygotes, (b) conversion of heterozygotes to mutant homozygotes, (c) marker rescue incorporation of mutant loci from these homozygotes into a non-mutagenized background, to produce "clean" heterozygotes, (d) tests for reversion of the heterozygotes. Initially, a model system (HGPRTase) will be used to test predicted characteristics of heterozygotes containing dominant alleles with partial penetrance.